Interpretive Summary: Our study tests whether healthy diets can prevent breast cancer. We study how factors present in such diets as soy and fruits (blueberry) can kill cells that form tumors. Results from these studies will help determine when and how healthy diets must be consumed to prevent formation of mammary tumors.

Technical Abstract:
Epidemiological evidence implicates diets rich in fruits and vegetables in breast cancer prevention due to their phytochemical components, yet mechanisms for their anti-tumor activities are not well-understood. A small population of mammary epithelial cells, termed cancer stem cells (CSC), may be responsible for initiating and sustaining tumor development. To evaluate dietary components that selectively target CSC and thus, provide mammary tumor protection, we utilized the estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB231 human breast cancer cell lines. Within 5 days of culture, both cell lines formed mammospheres at a frequency (1-2%) consistent with a subset of the cell population exhibiting stem cell-like characteristics. The soy isoflavone genistein dose-dependently decreased (40 nM > 2 µM) mammosphere numbers from both cell lines, relative to medium alone. A mixture of phenolic acids that include hippuric acid, ferrulic acid and 3-hydroxycinnamic acid, based on concentrations found in sera of rats fed diets containing 10% blueberry similarly inhibited mammosphere formation in MDA-MB231 but not in MCF-7 cells. By contrast, leptin and interleukin-6 had no activity in these cells. Results suggest that dietary factors may selectively target ER-positive and ER-negative cancer cells with stem-like properties in the prevention of breast cancer.